U-50,488H, a κ-opioid receptor agonist, markedly prevents memory dysfunctions induced by transient cerebral ischemia in mice

Abstract

Transient ischemia produced marked memory dysfunctions in mice on three different tasks, spontaneous alternation, elevated plus-maze and passive avoidance, as tested 1, 1–2, and 2–3 days after ischemic insult, respectively. U-50,488H, a κ-opioid receptor, agonist, administered 20 min before ischemic insult markedly prevented the impairment of spontaneous alternation, the prolongation of transfer latency in elevated-plus maze and the shortening of step-through latency in passive avoidance induced by transient ischemia. The protective effect of U-50,488H (30 mg/kg) on ischemia-induced memory dysfunctions observed in the three tasks was almost completely reversed by pretreatment with nor-binaltorphimine (4 μg, i.c.v.), a κ-selective opioid antagonist. Although U-50,488H (30 mg/kg) did not affect body temperature in sham mice, it blocked hypothermia induced by ischemic insult. These results suggest that the protective effect of U-50,488H on memory dysfunctions in the ischemic mice is associated with the activation of κ-opioid receptors and is not based upon hypothermia.